Osteoarthritis (OA) is an inflammatory condition for which there are currently no effective treatments. MSCs (Mesenchymal Stem/Stromal Cells) have been used successfully in pre-clinical models to resurface degenerated cartilage. Intra-Articular (IA) administration of MSCs reduces pain and protects or heals cartilage in early-stage clinical trials. However, the consistent lack of engraftment suggests that the observed effect is delivered via a “hit-and-run” mechanism, involving the temporal release of paracrine molecules.

MSCs produce a number of chemokines and cytokines that aid in the repair of damaged tissue, restoration of normal tissue metabolism, and most importantly, suppression of inflammation. Therapeutic factor secretion is increased in response to inflammatory signals or apoptosis induced by the host immune system. Trophic effectors are soluble molecules that are released or carried by extracellular vesicles. This review provides an overview of the functions and mechanisms of MSC-secreted molecules that have been found to be upregulated in OA models, whether in vitro or in vivo.